title: A chimeric dengue virus vaccine using Japanese encephalitis virus vaccine strain SA14-14-2 as backbone is immunogenic and protective against either parental virus in mice and nonhuman primates.
abstract: The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with ChinDENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.forename: Hui-Qiang
authors.initials: HQ
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Yu
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.forename: Hong-Jiang
authors.initials: HJ
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Yu
authors.forename: Zhong-Yu
authors.initials: ZY
authors.lastname: Liu
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014759:Viral Envelope Proteins